A microarray-based system for label-free, high throughput protein expression in profiling in very small volumes of tissue or blood (approximately 10 mL) is proposed. The system will consist of an instrument, and a proteomic biosensor chip integrated into a fluidics cartridge. It utilizes a novel grating-coupled surface plasmon resonance (GC-SPR) imaging technology that will enable measurement of thousands of analytes simultaneously without the limitations of reporter molecules. We will use rapid assessment of cellular activation in cell cultures as a model system to develop and evaluate the GC-SPR chip- based technology. We expect that this technology will provide a new powerful tool for metabolic and physiologic phenotyping of laboratory animals as well as for investigating the metabolic outcome of genetic variation in humans. It will be applicable to the detection of a broad range of metabolic products, signaling molecules, hormones, enzymes, receptors and other proteins. Examples include rapid measurement of cytokine profiles, simultaneous measurement of many hormone concentrations in tissue samples, and assessment of intracellular signal transduction cascades. The technology is also suitable for minimally invasive microarrays in clinical settings where diagnostic profiles could be measured from a drop of blood instead of a large sample from a vein. PROPOSED COMMERCIAL APPLICATIONS: Potential applications range from basic research to drug target discovery to clinical diagnostics. Specific examples include protein expression profiling; high-throughput ligand fishing, identifying new receptors and natural ligands, immune response characterization, homology studies on protein families, identifying disease markers and others.